Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion.
Sci Rep
; 7(1): 5958, 2017 07 20.
Article
em En
| MEDLINE
| ID: mdl-28729700
ABSTRACT
Neurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE complex required for membrane fusion and also increases the rate of exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and in hippocampal neurons. Recently a fungi-derived sphingosine homologue, FTY720, has been approved for treatment of multiple sclerosis. In its non-phosphorylated form FTY720 accumulates in the central nervous system, reaching high levels which could affect neuronal function. Considering close structural similarity of sphingosine and FTY720 we investigated whether FTY720 has an effect on regulated exocytosis. Our data demonstrate that FTY720 can activate vesicular synaptobrevin for SNARE complex formation and enhance exocytosis in neuroendocrine cells and neurons.
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1
Base de dados:
MEDLINE
Assunto principal:
Esfingosina
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Vesículas Sinápticas
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Proteínas R-SNARE
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Cloridrato de Fingolimode
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Esclerose Múltipla
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Sistemas Neurossecretores
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article